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Identifying the\u00a0dominant driver(s) is critical for treatment decision. We studied the relative dynamics of multiple oncogenic drivers in longitudinal plasma of 50\n                    <jats:italic>EGFR<\/jats:italic>\n                    \u2010mutant non\u2010small\u2010cell lung cancer patients receiving gefitinib and hydroxychloroquine. We performed digital PCR and targeted sequencing on samples from all patients and shallow whole\u2010genome sequencing on samples from three patients who underwent histological transformation to small\u2010cell lung cancer. In 43 patients with known EGFR mutations from tumour, we identified them accurately in plasma of 41 patients (95%, 41\/43). We also found additional mutations, including\n                    <jats:italic>EGFR<\/jats:italic>\n                    T790M (31\/50, 62%),\n                    <jats:italic>TP53<\/jats:italic>\n                    (23\/50, 46%),\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    (7\/50, 14%) and\n                    <jats:italic>PTEN<\/jats:italic>\n                    (4\/50, 8%). Patients with both\n                    <jats:italic>TP53<\/jats:italic>\n                    and\n                    <jats:italic>EGFR<\/jats:italic>\n                    mutations before treatment had worse overall survival than those with only\n                    <jats:italic>EGFR<\/jats:italic>\n                    . Patients who progressed without T790M had worse PFS during TKI continuation and developed alternative alterations, including small\u2010cell lung cancer\u2010associated copy number changes and\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations, that tracked subsequent treatment responses. Longitudinal plasma analysis can help identify dominant resistance mechanisms, including non\u2010druggable genetic information that may guide clinical management.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201707945","type":"journal-article","created":{"date-parts":[[2018,5,30]],"date-time":"2018-05-30T03:35:42Z","timestamp":1527651342000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Dynamics of multiple resistance mechanisms in plasma DNA during EGFR\u2010targeted therapies in non\u2010small cell lung cancer"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0595-6664","authenticated-orcid":false,"given":"Dana Wai Yi","family":"Tsui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed","family":"Murtaza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin Seng Cheong","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar M","family":"Rueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dineika","family":"Chandrananda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross A","family":"Soo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Liang","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boon Cher","family":"Goh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Caldas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Forshew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davina","family":"Gale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Marass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Eisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3289-8498","authenticated-orcid":false,"given":"Tan Min","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2825-4788","authenticated-orcid":false,"given":"Nitzan","family":"Rosenfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,5,30]]},"reference":[{"key":"BFEMMM201707945_CR1","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nature22364","volume":"545","author":"C Abbosh","year":"2017","unstructured":"Abbosh C, Birkbak NJ, Wilson GA, Jamal\u2010Hanjani M, Constantin T, Salari R, Le Quesne J, Moore DA, Veeriah S, Rosenthal R et\u00a0al (2017) Phylogenetic ctDNA analysis depicts early\u2010stage lung cancer evolution. 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